Symptoms
Gout is an inflammatory disease of the joints that manifests acutely in attacks of severe pain that worsens with pressure, touch, and movement. The joints are swollen with inflammation, and the skin is red and warm. Fever is observed. Gout often begins in the lower extremities and at the metatarsophalangeal joint (podagra). Urat crystals may deposit in tissues and joints and form visible nodules (tophi), eventually leading to deformity and limited mobility. Comorbidities such as high blood pressure and metabolic syndrome are common, and gout may be associated with serious complications such as cardiovascular disease. Other possible sequelae include kidney stones, kidney disease, and joint damage. Untreated gout may progressively worsen over time and affect multiple joints.
Causes
The cause of the disease is an elevated uric acid concentration in the blood (hyperuricemia, > 6.5-7.0 mg/dl serum), which leads to crystallization of sodium urate crystals, resulting in inflammatory reactions. However, asymptomatic hyperuricemia is common and should not be equated with gout, as it actually leads to the disease in only a minority of patients. Hyperuricemia results from increased formation or decreased excretion of uric acid by the kidney. The disturbance of excretion is of much greater importance. Uric acid is a breakdown product of the body’s purines (adenosine, guanosine), which are also present in some foods, e.g. meat, offal such as liver, seafood, sardines and mushrooms. Most mammals convert uric acid with uricase into the water-soluble allantoin, which is easily eliminated by the kidneys. In humans, this enzyme is absent because the corresponding gene is inactivated.
Risk factors
Possible risk factors include:
- Certain medications, e.g., diuretics, low-dose acetylsalicylic acid, ciclosporin
- A diet high in purines (meat), alcohol (especially beer, liquor), fructose.
- Kidney disease
- Dehydration
- A family burden
- The male gender
In women, the risk increases only after menopause. It is known that patients with metabolic syndrome (obesity, dyslipidemia, high blood pressure, high blood sugar) are more likely to suffer from gout.
Diagnosis
The diagnosis is made on the basis of the clinical presentation, a determination of uric acid in the serum, imaging techniques, and detection of urate crystals in the synovial fluid. Possible differential diagnoses include pseudogout, cellulitis, osteoarthritis, Lyme disease (Lyme arthritis), psoriatic arthritis and other arthritides, infectious diseases, and bursitis. According to the literature, the disease is often misdiagnosed.
Nonpharmacologic treatment
- Treat obesity and other risk factors. Weight should be reduced only slowly.
- Sufficient liquid to take
- Limit purine consumption
- Avoid alcohol and especially beer (high purine content) and liquor, a glass of wine is possible
- Avoid fructose-rich drinks, such as sodas.
- Physical exercise
- Adequate intake of dairy products and vitamin C. Coffee is also protective.
In the attack, the application of cool compresses is recommended to cool and relieve pain. The acute symptoms usually pass within 5-10 days even without treatment.
Drug treatment
Drug therapy should be initiated as soon as possible during an acute attack of gout. The goal is to eliminate the severe pain quickly and reliably. Nonsteroidal anti-inflammatory drugs such as indomethacin, ibuprofen, diclofenac, or naproxen are analgesic and anti-inflammatory. They are usually taken orally, but can also be applied locally. Acetylsalicylic acid is not recommended because it can increase uric acid levels. COX-2 inhibitors such as etoricoxib are also approved for this indication. Glucocorticoids such as prednisolone or prednisone are administered orally; methylprednisolone can also be injected directly into the affected joints Colchicine (Colchicum-Dispert, Germany) is suitable for treatment and prevention.When used, however, precautions must be carefully observed because of the narrow therapeutic range and the risk of intoxication see under Colchicine Opioids are exclusively analgesic and may be used adjunctively for severe pain.
Drug prevention
For prevention of recurrent gout attacks and elimination of deposits, the uricostatic drug allopurinol (Zyloric, generics) is considered the drug of choice. Its action is based on the inhibition of xanthine oxidase, which causes a decrease in the level of uric acid in the blood. Adverse effects include nausea, vomiting, and rarely severe hypersensitivity reactions. Treatment should be initiated only after an attack has completely resolved, otherwise the attack may worsen see under allopurinol An alternative is febuxostat (Adenuric), a xanthine oxidase inhibitor without a purine structure see under febuxostat The uricosuric probenecid (Santuril), which promotes renal excretion of uric acid, is less commonly used in practice. Benzbromarone (Desuric), also a uricosuric, is no longer available in many countries because of its liver toxicity. Sulfinpyrazone (Anturan) has also been unavailable in many countries for some time see under probenecid Losartan can be used in concomitant hypertension because it also has the property of promoting uric acid excretion. Pegloticase is a recombinant uricase approved for the treatment of severe gout. The enzyme catalyzes the formation of allantoin from uric acid (see above). Rasburicase (Fasturtec) is approved in many countries but has not been indicated for gout. URAT1 inhibitors: lesinurad (Zurampic) is a selective URAT1 inhibitor. It inhibits the reabsorption of uric acid at the kidney, promoting its excretion through the urine. Lesinurad is combined with allopurinol.
